Genome-wide association analyses of common infections in a large practice-based biobank.
Genome-wide association analyses of common infections in a large practice-based biobank.
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DOI：
10.1186/s12864-022-08888-9
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发表时间：
2022-09-27
期刊：
影响因子：
4.4
通讯作者：
Feng, QiPing
中科院分区：
文献类型：
--
作者：
Jiang, Lan;Kerchberger, V. Eric;Shaffer, Christian;Dickson, Alyson L.;Ormseth, Michelle J.;Daniel, Laura L.;Leon, Barbara G. Carranza;Cox, Nancy J.;Chung, Cecilia P.;Wei, Wei-Qi;Stein, C. Michael;Feng, QiPing
传染病是全世界发病率和死亡率的常见原因。对感染的易感性是高度可遗传的；然而，在确定常见传染病背后的遗传决定因素方面所做的工作很少。使用23andMe关于自我报告感染的信息进行了一次GWAS；我们开始确认以前的基因座并使用医学诊断的感染识别新的基因座。我们在Vanderbilt使用基于电子健康记录(EHR)的生物库和诊断代码来识别白人患者中12种传染病的病例：尿路感染、肺炎、慢性鼻窦感染、中耳炎、念珠菌病、链球菌性咽炎、带状疱疹、唇疱疹、乙肝、传染性单核细胞增多症、结核病(TB)或结核试验阳性和丙型肝炎。我们从没有候选疾病诊断代码的患者中选择对照，并在第一次和最后一次EHR就诊时按出生年份、性别和日历年进行匹配。我们使用SAIGE进行GWA，并使用S-PrediXcan进行转录组分析。我们还进行了表型全组关联研究，以了解已识别的遗传变异和临床表型之间的关联。我们复制了3个23andMe基因座(p ≤ 0.05)：带状疱疹和rs7047299-A(p = 2.6 × 10-3)和rs2808290-C(p = 9.6 × 10-3)；中耳炎和rs114947103-C(p = 0.04)。我们还发现了两个新的区域(p ≤ 5 × 10-8)：rs113235453-G(p = 3.04 × 10-8)和rs10422015-T(p = 3.11 × 10-8)。在第三产业中，有四个基因疾病关联显著：SLC30A9与中耳炎(p = 8.06 × 10-7)；LRP3和WDR88与念珠菌病(p = 3.91 × 10-7和p = 1.95 × 10-6)；AAMDC与乙肝(p = 1.51 × 10-6)。我们对12种传染病进行了GWAs和TWAs，并确定了新的传染病易感性的基因贡献者。网上版载有补充材料，可在10.1186/s12864-022-08888-9查阅。
Infectious diseases are common causes of morbidity and mortality worldwide. Susceptibility to infection is highly heritable; however, little has been done to identify the genetic determinants underlying common infectious diseases. One GWAS was performed using 23andMe information about self-reported infections; we set out to confirm previous loci and identify new ones using medically diagnosed infections. We used the electronic health record (EHR)-based biobank at Vanderbilt and diagnosis codes to identify cases of 12 infectious diseases in white patients: urinary tract infection, pneumonia, chronic sinus infections, otitis media, candidiasis, streptococcal pharyngitis, herpes zoster, herpes labialis, hepatitis B, infectious mononucleosis, tuberculosis (TB) or a positive TB test, and hepatitis C. We selected controls from patients with no diagnosis code for the candidate disease and matched by year of birth, sex, and calendar year at first and last EHR visits. We conducted GWAS using SAIGE and transcriptome-wide analysis (TWAS) using S-PrediXcan. We also conducted phenome-wide association study to understand associations between identified genetic variants and clinical phenotypes. We replicated three 23andMe loci (p ≤ 0.05): herpes zoster and rs7047299-A (p = 2.6 × 10–3) and rs2808290-C (p = 9.6 × 10–3;); otitis media and rs114947103-C (p = 0.04). We also identified 2 novel regions (p ≤ 5 × 10–8): rs113235453-G for otitis media (p = 3.04 × 10–8), and rs10422015-T for candidiasis (p = 3.11 × 10–8). In TWAS, four gene-disease associations were significant: SLC30A9 for otitis media (p = 8.06 × 10–7); LRP3 and WDR88 for candidiasis (p = 3.91 × 10–7 and p = 1.95 × 10–6); and AAMDC for hepatitis B (p = 1.51 × 10–6). We conducted GWAS and TWAS for 12 infectious diseases and identified novel genetic contributors to the susceptibility of infectious diseases. The online version contains supplementary material available at 10.1186/s12864-022-08888-9.
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影响因子：
56.3
作者：
Burgner, David;Jamieson, Sarra E.;Blackwell, Jenefer M.
通讯作者：
Blackwell, Jenefer M.
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
46.9
作者：
通讯作者：
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2型糖尿病和丙型肝炎病毒感染的风险：系统评价。
影响因子：
4.6
作者：
Guo X;Jin M;Yang M;Liu K;Li JW
通讯作者：
Li JW
影响因子：
3.8
作者：
Friederich MW;Perez FA;Knight KM;Van Hove RA;Yang SP;Saneto RP;Van Hove JLK
通讯作者：
Van Hove JLK